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RELYUBL SIGNED

Regulation of lymphocyte biology by ubiquitin and ubiquitin like modifiers

Total Cost €

0

EC-Contrib. €

0

Partnership

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 RELYUBL project word cloud

Explore the words cloud of the RELYUBL project. It provides you a very rough idea of what is the project "RELYUBL" about.

proteome    deterred    inform    discover    focussing    enzymes    modifiers    networks    regulating    systematically    inflammation    elucidate    mechanistic    full    hypothesize    give    cells    lymphocyte    complexity    lymphocytes    substantial    modifications    recognition    disrupted    limited    therapies    fundamentally    disease       adaptive    malignant    remove    components    ubl    insights    ptms    immunological    regulate    daunting    phosphorylation    function    focussed    regulated    dependent    tightly    roles    immunity    cell    immune    disorders    ultimately    ubiquitylation    autoimmunity    rewriting    biochemical    modified    intense    vivo    progress    biology    deregulation    area    posttranslational    lymphomas    mice    ub    tackled    implied    reveal    ubls    undiscovered    hence    predominantly    seeking    pathogens    events    unknown    ubiquitin    genetic    signalling    protein    activation    differentiation    severe    modules    proteins    protect    pioneer    dynamic    nodes   

Project "RELYUBL" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF DUNDEE 

Organization address
address: Nethergate
city: DUNDEE
postcode: DD1 4HN
website: www.dundee.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 1˙499˙987 €
 EC max contribution 1˙499˙987 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF DUNDEE UK (DUNDEE) coordinator 1˙499˙987.00

Map

 Project objective

T lymphocytes are key cells of the adaptive immune system that protect us against pathogens and malignant cells. T cell activation and differentiation are tightly controlled processes and deregulation can result in lymphomas, autoimmunity and inflammation. Hence, the biochemical events regulating lymphocyte biology have long been a topic of intense research, which has been focussed predominantly on protein phosphorylation. I hypothesize that there are crucial roles undiscovered in T cells for other posttranslational modifications (PTMs) such as ubiquitin (Ub) and Ub-like proteins (UBLs). The importance of ubiquitylation in adaptive immunity is implied by the severe immunological disorders observed when components of the Ub system are disrupted in lymphocytes. Genetic approaches in mice give a limited understanding about the roles of these modifiers and do not reveal the full extent to which Ub and UBLs regulate lymphocyte biology. Deterred by the complexity of the Ub system, the field has not yet tackled the daunting challenge of systematically investigating these modifiers in vivo. The goal of this proposal is to define how T cell function and immune responses are regulated by Ub and UBL signalling networks. To pioneer substantial progress in this area, we will develop new methods to identify and characterize currently unknown recognition modules for the different modifications. We will elucidate the Ub and UBL modified proteome in lymphocytes and characterize dynamic changes of these PTMs during T cell activation. By focussing on enzymes that remove the modifications we will discover how these PTMs are regulated and define Ub and UBL-dependent signalling nodes. Each phase of the work will deliver fundamentally novel mechanistic insights into these PTMs while rewriting current concepts of signalling in lymphocytes. Ultimately, this work will inform therapies seeking to target lymphocyte activity in disease.

 Publications

year authors and title journal last update
List of publications.
2018 Dominika Kwasna, Syed Arif Abdul Rehman, Jayaprakash Natarajan, Stephen Matthews, Ross Madden, Virginia De Cesare, Simone Weidlich, Satpal Virdee, Ivan Ahel, Ian Gibbs-Seymour, Yogesh Kulathu
Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability
published pages: 150-164.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.02.023
Molecular Cell 70/1 2019-05-01

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